NAME: SPECIMEN TYPE: Physician Name: COLLECTION DATE ... · statin-induced myopathy is not...

Comprehensive Pro�le

Test DetailsGene Genotype Phenotype Clinical Consequences

Apolipoprotein E ε3/ε4 Altered APOE function Not associated with type III hyperlipoproteinemia - Increased risk ofcardiovascular disease

COMT Val158Met A/A Low COMT Activity Consistent with a significantly reduced catechol O-methyltransferase (COMT)function.

CYP1A2 *1A/*1V Normal Metabolizer- Possible Inducibility

Consistent with a typical CYP1A2 activity in absence of inducing substances.Rapid metabolism may occur in presence of inducers such as barbiturates,cruciferous vegetables, carbamazepine, rifampin and smoking.

CYP2B6 *1/*6 Intermediate Metabolizer Consistent with a moderate deficiency in CYP2B6 activity. Potential risk for sideeffects or loss of efficacy with drug substrates.

CYP2C19 *1/*2 Intermediate Metabolizer Consistent with a moderate deficiency in CYP2C19 activity. Potential risk forside effects or loss of efficacy with drug substrates.

CYP2C9 *1/*1 Normal Metabolizer Consistent with a typical CYP2C9 activity. This test did not identify risks for sideeffects or loss of efficacy with drug substrates.

CYP2D6 *1/*1 Normal Metabolizer Consistent with a typical CYP2D6 activity. This test did not identify risks for sideeffects or loss of efficacy with drug substrates.

CYP3A4 *1/*1 Normal Metabolizer Consistent with a typical CYP3A4 activity. Caution is advised when prescribingnarrow therapeutic index drugs. Alternative drugs or dose adjustment may berequired if CYP3A inhibitors or inducers are co-prescribed.

CYP3A5 *3/*3 Poor Metabolizer Consistent with a poor CYP3A5 activity. This phenotype is the most common inthe general population. Caution is advised when prescribing narrow therapeuticindex drugs. Alternative drugs or dose adjustment may be required if CYP3Ainhibitors or inducers are co-prescribed.

F2F5

rs1799963 GGrs6025 CC

Normal Risk of Thrombosis Unless other genetic or circumstantial risk factors are present, the patient is notexpected to have an increased risk for thrombosis.

MTHFR c.665C>T GG Normal MTHFR Activity The patient does not carry the MTHFR C677T mutation (wild-type) and thepatient's MTHFR activity is normal. This is not associated with an increased riskof hyperhomocysteinemia.

MTHFR c.1286A>C GTc.665C>T GG

No Increased Risk of Hyperhomocysteinemia

The patient's MTHFR function is slightly reduced, and no significanthyperhomocysteinemia is expected.

OPRM1 A118G A/A Normal OPRM1 Function Consistent with a normal OPRM1 receptor signaling efficiency induced byexogenous opioids. This is associated with a good analgesia following standardopioid doses and a poor response to naltrexone.

SLCO1B1 521T>C T/T Normal Function Consistent with a typical SLCO1B1 transporter function. The patient's risk forstatin-induced myopathy is not increased.

TPMT *1/*3A Intermediate Metabolizer Consistent with a moderate deficiency in TPMT activity. Increased risk forserious side effects with conventional doses of thiopurines.

VKORC1 -1639G>A G/A Intermediate Warfarin Sensitivity

VKORC1 is the site of action of warfarin. The patient may require a decrease inwarfarin dosage.

Alleles Tested: Apolipoprotein E ε2, ε4, (ε3 is reference); COMT Val158Met; CYP1A2 *1C, *1D, *1E, *1F, *1J, *1K, *1L, *1V, *1W; CYP2B6 *5, *6, *7, *9, *16, *18,*22; CYP2C19 *2, *3, *4, *4B, *5, *6, *7, *8, *9, *10, *17; CYP2C9 *2, *3, *4, *5, *6, *11; CYP2D6 *2, *3, *4, *4M, *6, *7, *8, *9, *10, *12, *14A, *14B, *17, *29, *41, *5(gene deletion), XN (gene duplication); CYP3A4 *1B, *2, *3, *12, *17, *22; CYP3A5 *2, *3, *3B, *3C, *6, *7, *8, *9; Factor II rs1799963; Factor V Leiden rs6025;MTHFR c.1286A>C, c.665C>T; OPRM1 A118G; SLCO1B1 521T>C; TPMT *2, *3A, *3B, *3C, *4; VKORC1 -1639G>A

PROVIDER INFORMATIONSPECIMEN DETAILS

SPECIMEN TYPE:

COLLECTION DATE:

RECEIVED DATE:

REPORT DATE:

buccal swab10/16/201910/16/201910/17/2019

Physician Name: Clinic Name:

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16

Dallas, TX 752044225 O�ce Parkway, Suite 110

healthawarenessproject.orginfo@thehapllc.com386-319-9407AmeriHealth Laboratory

Risk Management

Type III HyperlipoproteinemiaNot Associated with Type III Hyperlipoproteinemia

Consider dietary adjustments (very low fat diet) and lipid-lowering therapy based on lipid profiles and other risk factors.

The APOE E3 is the normal APOE. The APOE E4 confers a limitation of HDL binding to its receptor, and is associated with increased plasmacholesterol, LDL, and triglycerides. Individuals that are heterozygous for this allele may have higher total cholesterol levels and elevatedLDL cholesterol levels. The APOE ε3/ε4 genotype is associated with an increased risk for developing atherosclerosis and cardiovasculardisease.

The patient is positive for the APOE c.388 T>C (Cys130Arg) mutation and negative for the APOE c.526 C>T (Arg176Cys) mutation. Thepatient's genotype is ε3/ε4 (frequency: 15-28%).

Hyperhomocysteinemia - DepressionNo Increased Risk of Hyperhomocysteinemia

Patients diagnosed with depression: as lower folate levels are associated with poorer antidepressant response, and baseline levels of folatewithin the normal range predict antidepressant response, testing for homocysteine levels and serum folate levels may be informative forthis patient before prescribing methylfolate as an antidepressant-augmenting agent.

Patients diagnosed with depression often have low folate levels and homocysteine is a highly sensitive marker of folate status. Functionalfolate deficiency is indicated by elevated homocysteine. With a normal MTHFR activity, this patient can process folate normally and isunlikely to have elevated plasma levels of homocysteine.

The patient does not carry the MTHFR c.665C>T variant. MTHFR enzyme activity is normal.

ThrombophiliaNormal Risk of Thrombosis

Assess thrombotic risk based on other genetic and/or circumstantial risk factors such as smoking, obesity, malignancy, prolongedimmobilization or surgery.

Estrogen-containing contraceptive and hormone replacement therapy: unless other genetic and/or circumstantial risk factors arepresent, consider standard prescribing and monitoring practices.

The patient's risk of thrombosis is not increased (average risk of clotting is about 1 in 1000 for anyone in a year). However, because thistest cannot find all of the inherited reasons for abnormal clotting, other factors may affect this risk assessment.

The patient does not carry the F5 c.1601G>A variant (also known as Factor V Leiden) or the F2 c.*97G>A variant (also known as Factor II20210G>A).

Hyperhomocysteinemia - ThrombosisNo Increased Risk of Hyperhomocysteinemia

The patient's MTHFR activity is slightly reduced.

The patient's slightly reduced MTHFR activity is not a risk factor for hyperhomocysteinemia. Unless other risk factors are present, thepatient is not expected to have an increased risk for venous thromboembolism (VTE).

The patient carries one copy of MTHFR c.1286A>C variant (heterozygous). MTHFR enzyme activity is reduced (80% of normal activity).

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Thioguanine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer)The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of thioguanine.

Nonmalignant indications Therapy initiation: if normal starting dose is ≥ 40-60mg/m2/day, consider starting with a 50-80% dose reduction and

adjust subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks toreach steady state after each dose adjustment. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is ≥ 40-60mg/m2/day, consider starting with a 50-80% dose reduction and

adjust subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks to reach steadystate after each dose adjustment.

These genotype results cannot be used to assess the patient's risk of thiopurine-related pancreatitis or hepatotoxicity.

ACTIONABLE

Tabloid®

Mercaptopurine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer)The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of mercaptopurine.

Nonmalignant indications Therapy initiation: if normal starting dose is 1.5mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks to reachsteady state after each dose adjustment. A dose reduction may not be needed when the initiation dose considered isbelow 1.5mg/kg/day. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is 75mg/m2/day (1.5mg/kg/day), consider starting with a 30-80% dose

reduction and adjust subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks toreach steady state after each dose adjustment.


ACTIONABLE

Purinethol®, Purixan®

Azathioprine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer) ACTIONABLE

Azasan®, Imuran®

TPMT Guidance

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of azathioprine.

Nonmalignant indications Therapy initiation: if normal starting dose is 2-3mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks to reachsteady state after each dose adjustment. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is 2-3mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks to reach steady stateafter each dose adjustment.


PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Potentially Impacted Medications

DRUG CLASS STANDARD PRECAUTIONS USE WITH CAUTION CONSIDER ALTERNATIVES

Anticancer Agents

Cardiovascular

CATEGORY

Antifolates Methotrexate (Trexall®)

Thiopurines

Azathioprine (Azasan®, Imuran®)Mercaptopurine (Purinethol®,

Purixan®)Thioguanine (Tabloid®)

Angiotensin II Receptor Antagonists

Azilsartan (Edarbi®, Edarbyclor®)Candesartan (Atacand®)Eprosartan (Teveten®)Irbesartan (Avapro®)

Losartan (Cozaar®, Hyzaar®)Olmesartan (Benicar®)Telmisartan (Micardis®)

Valsartan (Diovan®, Entresto®)

Antianginal Agents Ranolazine (Ranexa®)

Antiarrhythmics

Amiodarone (Nexterone®, Pacerone®)

Disopyramide (Norpace®)Flecainide (Tambocor®)

Mexiletine (Mexitil®)Propafenone (Rythmol®)Quinidine (Quinidine®)

Sotalol (Betapace®, Sorine®, Sotylize®)

Anticoagulants

Apixaban (Eliquis®)Betrixaban (Bevyxxa®)

Dabigatran Etexilate (Pradaxa®)Edoxaban (Savaysa®)

Fondaparinux (Arixtra®)Rivaroxaban (Xarelto®)Warfarin (Coumadin®)

AntiplateletsPrasugrel (Effient®)Ticagrelor (Brilinta®)

Vorapaxar (Zontivity®)Clopidogrel (Plavix®)

Beta Blockers

Atenolol (Tenormin®)Bisoprolol (Zebeta®)Carvedilol (Coreg®)

Labetalol (Normodyne®, Trandate®)

Metoprolol (Lopressor®)Nebivolol (Bystolic®)

Propranolol (Inderal®)Timolol (Timoptic®)

Diuretics Torsemide (Demadex®)

PATIENT INFORMATION

DOB:

SEX:

NAME: SAMPLE ID:

of 16




Diabetes

Gastrointestinal

Infections

CATEGORY

Statins

Atorvastatin (Lipitor®)Fluvastatin (Lescol®)

Lovastatin (Mevacor®, Altoprev®, Advicor®)

Pitavastatin (Livalo®)Pravastatin (Pravachol®)Rosuvastatin (Crestor®)

Simvastatin (Zocor®)

MeglitinidesNateglinide (Starlix®)

Repaglinide (Prandin®, Prandimet®)

Sulfonylureas

Chlorpropamide (Diabinese®)Glimepiride (Amaryl®)Glipizide (Glucotrol®)

Glyburide (Micronase®)Tolbutamide (Orinase®)

Antiemetics

Aprepitant (Emend-oral®)Dolasetron (Anzemet®)Dronabinol (Marinol®)

Fosaprepitant (Emend-i.v®)Fosnetupitant-Palonosetron

(Akynzeo-i.v®)Granisetron (Sancuso®, Sustol®)

Metoclopramide (Reglan®)Netupitant-Palonosetron (Akynzeo-

oral®)Ondansetron (Zofran®, Zuplenz®)

Palonosetron (Aloxi®)Rolapitant (Varubi®)

Proton Pump Inhibitors

Dexlansoprazole (Dexilant®, Kapidex®)

Esomeprazole (Nexium®)Lansoprazole (Prevacid®)Omeprazole (Prilosec®)

Pantoprazole (Protonix®)Rabeprazole (Aciphex®)

Antifungals

Amphotericin B (AmBisome®, Abelcet®)

Anidulafungin (Eraxis®)Caspofungin (Cancidas®)Fluconazole (Diflucan®)

Isavuconazonium (Cresemba®)Itraconazole (Sporanox®)Micafungin (Mycamine®)Posaconazole (Noxafil®)Voriconazole (Vfend®)

Anti-HIV Agents

Dolutegravir (Tivicay®, Triumeq®)Doravirine (Pifeltro®)Etravirine (Edurant®)

Raltegravir (Isentress®, Dutrebis®)Rilpivirine (Intelence®)

Efavirenz (Sustiva®)

Antimalarials Proguanil (Malarone®)

PATIENT INFORMATION

DOB:

SEX:

NAME: SAMPLE ID:

of 16




Pain

CATEGORY

Fibromyalgia Agents Milnacipran (Savella®)

Muscle Relaxants

Carisoprodol (Soma®)Cyclobenzaprine (Flexeril®,

Amrix®)Metaxalone (Skelaxin®)

Methocarbamol (Robaxin®)Tizanidine (Zanaflex®)

NSAIDs

Celecoxib (Celebrex®)Diclofenac (Voltaren®)Flurbiprofen (Ansaid®)

Ibuprofen (Advil®, Motrin®)Indomethacin (Indocin®)

Ketoprofen (Orudis®)Ketorolac (Toradol®)Meloxicam (Mobic®)

Nabumetone (Relafen®)Naproxen (Aleve®)

Piroxicam (Feldene®)Sulindac (Clinoril®)

Opioids

Alfentanil (Alfenta®)Benzhydrocodone (Apadaz®)

Buprenorphine (Butrans®, Buprenex®)

Codeine (Codeine; Fioricet® with Codeine)

Dihydrocodeine (Synalgos-DC®)Fentanyl (Actiq®)

Hydrocodone (Vicodin®)Hydromorphone (Dilaudid®,

Exalgo®)Levorphanol (Levo Dromoran®)

Meperidine (Demerol®)Oxycodone (Percocet®,

Oxycontin®)Oxymorphone (Opana®,

Numorphan®)Sufentanil (Sufenta®)

Tapentadol (Nucynta®)Tramadol (Ultram®)

Methadone (Dolophine®)Morphine (MS Contin®)

Antiaddictives Lofexidine (Lucemyra®)Bupropion (Wellbutrin®, Zyban®,

Aplenzin®, Contrave®)Naltrexone (Vivitrol®, Contrave®)

Anti-ADHD AgentsClonidine (Kapvay®)

Guanfacine (Intuniv®)

Amphetamine (Adderall®, Evekeo®)

Atomoxetine (Strattera®)Dexmethylphenidate (Focalin®)

Dextroamphetamine (Dexedrine®)

Lisdexamfetamine (Vyvanse®)Methylphenidate (Ritalin®, Aptensio XR®, Concerta®,

Metadate ER®, Quillivant ER®)

PATIENT INFORMATION

DOB:

SEX:

NAME: SAMPLE ID:

of 16




Psychotropic

CATEGORY

Anticonvulsants

Brivaracetam (Briviact®)Cannabidiol (Epidiolex®)

Carbamazepine (Tegretol®, Carbatrol®, Epitol®)

Eslicarbazepine (Aptiom®)Ethosuximide (Zarontin®)

Ezogabine (Potiga®)Felbamate (Felbatol®)

Fosphenytoin (Cerebyx®)Gabapentin (Neurontin®)

Lacosamide (Vimpat®)Lamotrigine (Lamictal®)Levetiracetam (Keppra®)

Oxcarbazepine (Trileptal®, Oxtellar XR®)

Perampanel (Fycompa®)Phenytoin (Dilantin®)Pregabalin (Lyrica®)

Rufinamide (Banzel®)Tiagabine (Gabitril®)

Topiramate (Topamax®)Valproic Acid (Depakote®,

Depakene®)Vigabatrin (Sabril®)

Phenobarbital (Luminal®)Primidone (Mysoline®)

Zonisamide (Zonegran®)

Antidementia AgentsDonepezil (Aricept®)

Galantamine (Razadyne®)Memantine (Namenda®)

Antidepressants

Amitriptyline (Elavil®)Amoxapine (Amoxapine®)

Citalopram (Celexa®)Clomipramine (Anafranil®)Desipramine (Norpramin®)Desvenlafaxine (Pristiq®)

Doxepin (Silenor®)Duloxetine (Cymbalta®)Escitalopram (Lexapro®)

Fluoxetine (Prozac®, Sarafem®)Fluvoxamine (Luvox®)Imipramine (Tofranil®)

Levomilnacipran (Fetzima®)Maprotiline (Ludiomil®)Mirtazapine (Remeron®)Nefazodone (Serzone®)Nortriptyline (Pamelor®)

Paroxetine (Paxil®, Brisdelle®)Protriptyline (Vivactil®)

Sertraline (Zoloft®)Trazodone (Oleptro®)

Trimipramine (Surmontil®)Venlafaxine (Effexor®)Vilazodone (Viibryd®)

Vortioxetine (Trintellix®)

PATIENT INFORMATION

DOB:

SEX:

NAME: SAMPLE ID:

of 16




Rheumatology

Transplantation

Urologicals

CATEGORY

Antipsychotics

Aripiprazole (Abilify®, Aristada®)Asenapine (Saphris®)

Brexpiprazole (Rexulti®)Cariprazine (Vraylar®)

Chlorpromazine (Thorazine®)Clozapine (Clozaril®)

Fluphenazine (Prolixin®)Haloperidol (Haldol®)Iloperidone (Fanapt®)

Loxapine (Loxitane®, Adasuve®)Lurasidone (Latuda®)

Olanzapine (Zyprexa®)Paliperidone (Invega®)

Perphenazine (Trilafon®)Pimavanserin (Nuplazid®)

Pimozide (Orap®)Quetiapine (Seroquel®)Risperidone (Risperdal®)Thioridazine (Mellaril®)Thiothixene (Navane®)

Trifluoperazine (Stelazine®)Ziprasidone (Geodon®)

BenzodiazepinesAlprazolam (Xanax®)

Clonazepam (Klonopin®)Diazepam (Valium®)

Clobazam (Onfi®)

Other Neurological Agents

Deutetrabenazine (Austedo®)Dextromethorphan / Quinidine

(Nuedexta®)Flibanserin (Addyi®)

Valbenazine (Ingrezza®)

Tetrabenazine (Xenazine®)

Anti-Hyperuricemics and Anti-Gout Agents

Colchicine (Mitigare®)Febuxostat (Uloric®)

ImmunomodulatorsApremilast (Otezla®)Tofacitinib (Xeljanz®) Leflunomide (Arava®)

Immunosuppressants Tacrolimus (Prograf®)

5-Alpha ReductaseInhibitors for BenignProstatic Hyperplasia

Dutasteride (Avodart®)Finasteride (Proscar®)

Alpha-Blockers for Benign Prostatic

Hyperplasia

Alfuzosin (UroXatral®)Doxazosin (Cardura®)Silodosin (Rapaflo®)

Tamsulosin (Flomax®)Terazosin (Hytrin®)

Antispasmodics for Overactive Bladder

Darifenacin (Enablex®)Fesoterodine (Toviaz®)

Mirabegron (Myrbetriq®)Oxybutynin (Ditropan®)Solifenacin (Vesicare®)Tolterodine (Detrol®)Trospium (Sanctura®)

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



DRUG CLASS STANDARD PRECAUTIONS USE WITH CAUTION CONSIDER ALTERNATIVESCATEGORY

Phosphodiesterase Inhibitors for Erectile

Dysfunction

Avanafil (Stendra®)Sildenafil (Viagra®)Tadalafil (Cialis®)

Vardenafil (Levitra®)

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Dosing Guidance

Clopidogrel Reduced Response to Clopidogrel (CYP2C19: Intermediate Metabolizer)

Consider alternative therapy. Examples of alternative drugs: prasugrel (contraindicated in TIA/Stroke patients), ticagrelor,aspirin, aspirin plus dipyridamole.

ACTIONABLE

Plavix®

Azathioprine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer)The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of azathioprine.

Nonmalignant indications Therapy initiation: if normal starting dose is 2-3mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks to reachsteady state after each dose adjustment. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is 2-3mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks to reach steady stateafter each dose adjustment.


ACTIONABLE

Azasan®, Imuran®

Mercaptopurine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer)The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of mercaptopurine.

Nonmalignant indications Therapy initiation: if normal starting dose is 1.5mg/kg/day, consider starting with a 30-80% dose reduction and adjust

subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks to reachsteady state after each dose adjustment. A dose reduction may not be needed when the initiation dose considered isbelow 1.5mg/kg/day. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is 75mg/m2/day (1.5mg/kg/day), consider starting with a 30-80% dose

reduction and adjust subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks toreach steady state after each dose adjustment.


ACTIONABLE

Purinethol®, Purixan®

Tetrabenazine Normal Sensitivity to Tetrabenazine (CYP2D6: Normal Metabolizer)For treating chorea associated with Huntington’s disease: Individualization of dose with careful weekly titration isrequired. The first week's starting dose is 12.5 mg daily; second week, 25 mg (12.5 mg twice daily); then slowly titrate atweekly intervals by 12.5 mg to a tolerated dose. The maximum daily dose in CYP2D6 normal metabolizers is 100mg, with a maximum single dose of 37.5 mg . If serious adverse events occur, titration should be stopped and thedose of tetrabenazine should be reduced. If the adverse event(s) do not resolve, consider withdrawal of tetrabenazine.

ACTIONABLE

Xenazine®

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Thioguanine Increased Risk of Myelotoxicity (TPMT: Intermediate Metabolizer)

The TPMT genotype results for this patient are indicative of a *1/*3A predicting intermediate TPMT activity. However,there is a small risk (<1 in 100,000) that this patient's genotype is instead *3B/*3C which would predict a low TPMTactivity. A TPMT phenotype test could distinguish between these possible phenotypes.

Evidence shows that 30 to 60% of patients with these genotype results experience severe leukopenia, neutropenia ormyelosuppression with standard doses of thioguanine.

Nonmalignant indications Therapy initiation: if normal starting dose is ≥ 40-60mg/m2/day, consider starting with a 50-80% dose reduction and

adjust subsequent doses based on disease-specific guidelines and/or myelosuppression, as needed. Allow 2-4 weeks toreach steady state after each dose adjustment. Alternative medications may also be considered.

Malignant indications Therapy initiation: if normal starting dose is ≥ 40-60mg/m2/day, consider starting with a 50-80% dose reduction and

adjust subsequent doses based on disease-specific guidelines and myelosuppression. Allow 2-4 weeks to reach steadystate after each dose adjustment.


ACTIONABLE

Tabloid®

Clobazam Possible Sensitivity to Clobazam (CYP2C19: Intermediate Metabolizer)In CYP2C19 intermediate metabolizers, plasma levels of the active metabolite N-desmethylclobazam were 2-fold higherthan those found in CYP2C19 normal metabolizers. The dose adjustment for intermediate metabolizers is not wellestablished, and therefore the recommendation for poor metabolizers is proposed. The starting dose should be 5mg/day, and dose titration should proceed slowly according to weight. Patients should be titrated initially to 10 mg /day(≤30 kg body weight) or 20 mg/day (>30 kg body weight). If necessary and based upon clinical response, an additionaltitration to the maximum doses 20 mg/day (≤30 kg body weight) or 40 mg/day (>30 kg body weight) may be startedon day 21.

ACTIONABLE

On�®

Efavirenz Increased Efavirenz Exposure (CYP2B6: Intermediate Metabolizer)The genotype result indicates that the patient is likely to have higher dose-adjusted trough concentrations of efavirenzfollowing standard dosing. This may result in increased risk of CNS adverse events. Consider initiating efavirenz with adecreased dose of 400 mg/day. If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed,consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggestedtherapeutic range (~1 to 4 µg/mL).

ACTIONABLE

Sustiva®

Atomoxetine Possible Atomoxetine Underexposure Leading to Decreased Response (CYP2D6: Normal Metabolizer)The genotype result indicates that the patient is likely to have an insufficient response due to inadequate drug exposurefollowing standard dosing. Consider the following dosing strategy:

Initiate treatment at 40 mg/day, increase to 80 mg/day after 3 days and maintain dose.•If after 2 weeks, optimal clinical response is not observed and adverse events are not present, consider a doseincrease to 100 mg/day.

•

If after 2 weeks, optimal clinical response is not observed and adverse events are not present, considertherapeutic drug monitoring 1-2 hours post dose. If the plasma concentration is less than 200 ng/ml consider adose increase to a target of 400 ng/ml. Doses greater than 100 mg/day may be needed to achieve a targetedtherapeutic concentration. (Therapeutic range: 200-1000 ng/ml).

•

ACTIONABLE

Strattera®

Morphine Altered Response to Morphine (COMT: Low COMT Activity)The patient carries two COMT Val158Met variants, which translates to a reduced COMT function. The patient mayrequire lower doses of morphine for adequate pain control. The dosing regimen needs to be individualized for eachpatient, taking into account the patient's prior analgesic treatment experience.

INFORMATIVE

MS Contin®

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Zonisamide Possible Sensitivity to Zonisamide (CYP2C19: Intermediate Metabolizer)

CYP2C19 is partly involved in the metabolism of zonisamide, and although preliminary studies show that CYP2C19intermediate metabolizers have a slightly lower (15%) zonisamide clearance than normal metabolizers, no significantchange in the clinical outcome has been reported with this antiepileptic drug. Therefore, zonisamide can be prescribedat standard label-recommended dosage and administration with a closer monitoring for adverse events.

INFORMATIVE

Zonegran®

Phenobarbital Possible Sensitivity to Phenobarbital (CYP2C19: Intermediate Metabolizer)CYP2C19 is partly involved in the metabolism of phenobarbital, and although CYP2C19 intermediate metabolizers havea lower clearance of phenobarbital than normal metabolizers, no significant changes in clinical outcome has beenreported with this antiepileptic drug. Therefore, phenobarbital can be prescribed at standard label-recommendeddosage and administration with a closer monitoring for adverse events.

INFORMATIVE

Luminal®

Primidone Possible Sensitivity to Primidone (CYP2C19: Intermediate Metabolizer)CYP2C19 is partly involved in the metabolism of primidone, and although CYP2C19 intermediate metabolizers have alower clearance of phenobarbital (active metabolite) than normal metabolizers, no significant changes in clinicaloutcome has been reported with this antiepileptic drug. Therefore, primidone can be prescribed at standard label-recommended dosage and administration with a closer monitoring for adverse events.

INFORMATIVE

Mysoline®

Naltrexone Altered Response to Naltrexone (OPRM1: Normal OPRM1 Function)Treatment of alcohol dependence: the patient has the OPRM1 118AA wild-type genotype that is associated with apoorer outcome with naltrexone therapy. Naltrexone-treated patients not carrying the OPRM1 118A>G G allele are lesslikely to respond to this drug, and may have higher relapse rates than those who are carriers of this allele. Thisassociation has not been reported consistently across studies.

INFORMATIVE

Vivitrol®, Contrave®

Methylphenidate Poor Response to Methylphenidate (COMT: Low COMT Activity)The patient's genotype result predicts a reduced therapeutic response to methylphenidate. Dosage should beindividualized according to the needs and response of the patient. Therapy should be initiated in small doses, withgradual weekly increments.

INFORMATIVE

Ritalin®, Aptensio XR®, Concerta®, Metadate ER®, Quillivant ER®

Dexmethylphenidate

Poor Response to Dexmethylphenidate (COMT: Low COMT Activity)

The patient's genotype result predicts a reduced therapeutic response to dexmethylphenidate. Dosage should beindividualized according to the needs and response of the patient. Therapy should be initiated in small doses, withgradual weekly increments.

INFORMATIVE

Focalin®

Le�unomide Increased Exposure to Le�unomide (CYP2C19: Intermediate Metabolizer)Leflunomide is metabolized by CYP2C19 and CYP1A2 to its active metabolite teriflunomide. Preliminary studies indicatethat patients with decreased CYP2C19 activity have a higher risk of developing gastrointestinal side effects andhepatotoxicity. There is insufficient data to calculate dose adjustment. If leflunomide is prescribed at standard dosing,monitor closely the patient's response and be alert to increased side effects.

Full blood cell count (CBC) and liver function parameters should be checked no more than 6 months before beginningtreatment, and every month for the initial 6 months of therapy. Blood pressure should be checked before beginningtreatment and periodically thereafter.

INFORMATIVE

Arava®

Methadone Increased Methadone Exposure (CYP2B6: Intermediate Metabolizer) INFORMATIVE

Dolophine®

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



The patient's genotype may be associated with an increased methadone exposure following standard dosing.

For Addiction Treatment : There is limited evidence indicating that intermediate metabolizers require lower doses,therefore, a dose adjustment cannot be calculated.

For Pain Management : There are no studies documenting the effect of CYP2B6 genetic variations on methadoneexposure when this drug is used as an analgesic. Consider standard prescribing and monitoring practices.

Lisdexamfetamine Poor Response to Lisdexamfetamine (COMT: Low COMT Activity)

The patient's genotype result predicts a reduced therapeutic response to amphetamine stimulants. If prescribed,lisdexamfetamine should be administered at the lowest effective dose, and dosage should be individually adjusted.

INFORMATIVE

Vyvanse®

Dextroamphetamine Poor Response to Dextroamphetamine (COMT: Low COMT Activity)

The patient's genotype result predicts a reduced therapeutic response to amphetamine stimulants. If prescribed,dextroamphetamine should be administered at the lowest effective dose, and dosage should be individually adjusted.

INFORMATIVE

Dexedrine®

Bupropion Altered Bupropion Exposure (CYP2B6: Intermediate Metabolizer)The genotype result indicates that the patient is likely to have increased bupropion exposure, but decreased exposureto the active metabolite (hydroxybupropion). This metabolite contributes to the therapeutic effects of bupropion whenused as a smoking cessation agent or as an antidepressant. This decrease in exposure of hydroxybupropion may resultin decreased therapeutic efficacy.

Smoking Cessation : There is insufficient data to allow calculation of dose adjustment. Consider standard prescribingand closer monitoring.

Major Depressive Disorder and Prevention of Seasonal A�ective Disorder : There is insufficient data to allowcalculation of dose adjustment. Therapeutic monitoring of bupropion-hydroxybupropion levels may be considered toguide dosing adjustments.

INFORMATIVE

Wellbutrin®, Zyban®, Aplenzin®, Contrave®

Amphetamine Poor Response to Amphetamine salts (COMT: Low COMT Activity)

The patient's genotype result predicts a reduced therapeutic response to amphetamine stimulants. If prescribed,amphetamines should be administered at the lowest effective dose, and dosage should be individually adjusted.

INFORMATIVE

Adderall®, Evekeo®

A medication has potentially reduced efficacy, increasedtoxicity or the patient has an increased risk for theindicated condition.

Guidelines exist for adjusting dosage, increased vigilance orthe patient has a moderate risk for the indicated condition.

The medication can be prescribed according to standardregimens or the patient's risk for the indicated condition isnot increased.

ACTIONABLE

Recommendations based upon publications by international pharmacogenetic expert groups, consortia or regulatory bodies (CPIC, DPWG, FDA, EMA). Recommendations are suitable for implementation in a clinical setting. Guidelines may change as knowledge arises.

INFORMATIVE

There are insufficient or contradictory findings documenting the impact of a given genetic polymorphism or drug interaction. Recommendations are informative and implementation in a clinical setting is optional.

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Methodology: This Micro-Array-based assay was developed to detect mutational changes within speci�c genes, including the most common and many of the more rarevariants for each gene analyzed. The Analytical Sensitivity and Speci�city for each mutation detected has been shown to be >99%.

Limitations of the Test: This test will not detect all the polymorphisms that could a�ect each gene target. Rare unknown genetic variations among individual patients mayoccur. The absence of a detectable gene mutation does not rule out the possibility that a patient may have an altered phenotype due to the presence of an undetectedpolymorphism. In addition, such rare events could in�uence other clinical factors such as drug-drug interactions, comorbidities or lifestyle habits.

Test Validation: Access Dx Laboratories has developed this pharmacogenetic test. The performance characteristics of this test were determined by Access Dx. The test hasnot been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such approval is not required. The independent validation ofthis assay by Access is compliant with all federal, state, and local regulations.

Translational Software Disclaimer: The information presented on this report is provided as general educational health information. The content is not intended to be asubstitute for professional medical advice, diagnosis, or treatment. Only a physician, pharmacist or other healthcare professional should advise a patient on the use of themedications prescribed.

The pharmacogenetic assay involves use of reporting software and genotype-phenotype associations performed by Translational Software(www.translationalsoftware.com). The software has not been evaluated by the Food and Drug Administration. The software, and the report generated by the software, isnot intended to diagnose, treat, cure, or prevent any disease. A quali�ed designee within the lab uses Translational Software to generate and subsequently review thereport. The pharmacogenetic report is one of multiple pieces of information that clinicians should consider in guiding their therapeutic choice for each patient. It remainsthe responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to dose guidelines does not necessarily assure a successfulmedical outcome.

Approved By:

PATIENT INFORMATION

NAME:

DOB:

SEX:

SAMPLE ID:

of 16



Patient Information CardThis is a summary genetic report for your patient to share with other healthcare providers. The card can be cut out along the dashed line and carried with the patient.

CYP2C19 *1/*2 Intermediate MetabolizerCYP2C9 *1/*1 Normal MetabolizerCYP2D6 *1/*1 Normal MetabolizerCYP3A4 *1/*1 Normal MetabolizerCYP3A5 *3/*3 Poor Metabolizer

Pharmacogenetic Test Summary

Patient:

ACC #:DOB:

REPORT DETAILS

MTHFR c.665C>T GG Normal MTHFR Activity

MTHFR c.1286A>C GTc.665C>T GG

No Increased Risk of Hyperhomocysteinemia

VKORC1 -1639G>A G/A Intermediate Warfarin Sensitivity

For a complete report contact The Health Awareness Project https://healthawarenessproject.org

PATIENT INFORMATION

DOB:

SEX:

NAME: SAMPLE ID:

of 16



NAME: SPECIMEN TYPE: Physician Name: COLLECTION DATE ... · statin-induced myopathy is not...

Documents

Transcript of NAME: SPECIMEN TYPE: Physician Name: COLLECTION DATE ... · statin-induced myopathy is not...